Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice
Details
Serval ID
serval:BIB_A5C5D601D53E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice
Journal
Journal of Cell Biology
ISSN
0021-9525 (Print)
Publication state
Published
Issued date
12/2000
Volume
151
Number
7
Pages
1583-90
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 25
Research Support, Non-U.S. Gov't --- Old month value: Dec 25
Abstract
Calpain 3 is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. It was previously shown that defects in the human calpain 3 gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly the proximal limb muscles. To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we generated capn3-deficient mice by gene targeting. capn3-deficient mice are fully fertile and viable. Allele transmission in intercross progeny demonstrated a statistically significant departure from Mendel's law. capn3-deficient mice show a mild progressive muscular dystrophy that affects a specific group of muscles. The age of appearance of myopathic features varies with the genetic background, suggesting the involvement of modifier genes. Affected muscles manifest a similar apoptosis-associated perturbation of the IkappaBalpha/nuclear factor kappaB pathway as seen in LGMD2A patients. In addition, Evans blue staining of muscle fibers reveals that the pathological process due to calpain 3 deficiency is associated with membrane alterations.
Keywords
Animals
*Apoptosis
Calpain/chemistry/*deficiency/genetics/metabolism
Creatine Kinase/metabolism
Crosses, Genetic
DNA-Binding Proteins/*metabolism
Evans Blue
Female
Fertility
Gene Deletion
Gene Targeting
Genotype
*I-kappa B Proteins
Male
Mice
Mice, Knockout
Muscle Fibers/enzymology/metabolism/pathology
Muscle, Skeletal/enzymology/metabolism/pathology
Muscular Dystrophies/*enzymology/genetics/*metabolism/pathology
NF-kappa B/*metabolism
Phenotype
RNA, Messenger/analysis/genetics
Sarcolemma/pathology
*Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 17:17
Last modification date
20/08/2019 16:10